CE / CME
Pharmacists: 0.75 contact hour (0.075 CEUs)
Nurses: 0.75 Nursing contact hour
Physicians: Maximum of 0.75 AMA PRA Category 1 Credit™
Released: August 09, 2023
Expiration: August 08, 2024
Special Considerations for Managing AEs of Therapies in Patients With Endometrial Cancer
Eva Y. Pan, PharmD, BCOP:
In the past few years, novel treatment options and combinations have entered the treatment landscape for endometrial cancer.
The combination of pembrolizumab plus lenvatinib is now commonly used in patients with MMR-proficient advanced/recurrent endometrial cancer experiencing failure on first-line carboplatin and paclitaxel chemotherapy. The inherent toxicities of this novel treatment regimen mean that, to keep patients safe, HCPs need to ensure that the patient and healthcare team understand lenvatinib- and immunotherapy-related safety concerns. After the combination of lenvatinib and pembrolizumab became the standard of care in relapsed/recurrent MMR-proficient endometrial cancer,3,4 we observed that lenvatinib can be challenging for most patients to tolerate. This also was reported in the phase III KEYNOTE-775 clinical trial evaluating lenvatinib plus pembrolizumab. With this treatment, patients can experience significant fatigue and myelosuppression, as well as severe hypertension (overall 65%, grade ≥3 39.2%), among other serious toxicities noted in the table on the right.17
At our center, we keep track of patients who are starting lenvatinib plus pembrolizumab for MMR-proficient recurrent endometrial cancer, and they are instructed to get a blood pressure cuff (if they do not already have one) and to record their blood pressure every day for the first 2 weeks after starting therapy. Our nurse team will take turns calling patients to check on their blood pressure because of the concern for hypertension with lenvatinib.4 If their blood pressure is concerning, they may need a referral to a cardiologist plus a prescription for antihypertensive medication.
Anecdotally, we have noticed that slightly more Black patients have had lenvatinib dose reductions because of blood pressure concerns. We also have had to start many patients on generic blood pressure medication (eg, amlodipine) because of lenvatinib use, but fortunately I have not heard of any issues of affordability for add-on antihypertensives. If insurance providers do not fully cover the cost of add-on medication or the copay is very high, for example, we are able to check the 340B pricing, which is a federal drug pricing program that allows qualifying hospitals and clinics that treat low-income and uninsured or underinsured individuals to purchase outpatient prescriptions at a discount of 25% to 50%.
Regarding immune-related adverse events (AEs), together with the National Comprehensive Cancer Network, Clinical Care Options has developed an Interactive Decision Support Tool to help HCPs manage toxicities associated with immune checkpoint inhibitor therapies for the treatment of various cancers while considering specific patient characteristics. The tool will ask users to enter specific patient characteristics such as organ system and toxicity grade and in turn will provide immune-related AE management recommendations tailored to that patient.
It is critical for HCPs to counsel and stay connected with patients about toxicities associated with their treatments and—if they stop filling their prescription—to have an open conversation about any AEs they may have experienced or affordability concerns.
Maria Avila-Wallace, NP:
Patients who are eligible to receive immunotherapy for recurrent or metastatic endometrial cancer meet with a gynecologic oncologist and have a consultation about treatments. Nurse practitioners (NPs) and physician associates (PAs) have one-on-one teaching sessions with patients regarding commonly reported treatment AEs, prompt identification of life-altering AEs and AEs of concern, which AEs merit a clinic visit, how to access the care team via phone or email, and how to communicate with the nursing staff.
All patient communications are available to all nursing staff, including NPs and PAs, via the hospital health portal or phone messages, allowing for prompt identification and management of treatment-related AEs. We frequently have posttherapy status checks, telehealth and follow-up phone calls, and e-consults and assess for urgent care visits. NPs and PAs also can prescribe supportive and add-on recommended therapies and offer strategies to help patients remain on therapy with lower incidence of dose reductions or discontinuation.
Patients receiving pembrolizumab or dostarlimab are carefully monitored for immune-related AEs, for example, thyroid dysfunctions and endocrinopathies, fatigue, pneumonitis, and colitis. We have institutional protocols in place for immediate management and criteria for multidisciplinary care and referrals. We offer outreach and patient navigation programs that assist vulnerable patients with access and in making and attending medical appointments. I talk to patients about holding therapy for grade 2/3 AEs and promptly involve the attending physician for potential life-threatening grade 4 toxicities.
For patients with MMR-proficient disease who are receiving combination therapy with pembrolizumab and lenvatinib, we also prescribe blood pressure cuffs and educate them on proper measuring and frequency of monitoring their blood pressure, emphasizing what is considered urgent reporting, and quickly start them on hypertension therapies as indicated. Most of our patients begin lenvatinib therapy at a lower dose of 8-14 mg because of preexisting comorbidities, Eastern Cooperative Oncology Group performance status, and symptomatology.
Resources are available to help patients identify common AEs associated with various therapies used to treat gynecologic cancers, including what to expect and when to call their healthcare team.
Special Considerations for Managing AEs of Therapies in Patients With Ovarian Cancer
Eva Y. Pan, PharmD, BCOP:
The key AEs associated with PARP inhibitors in patients with previously untreated advanced or recurrent epithelial ovarian cancer are hematologic and include anemia, neutropenia, and thrombocytopenia.18-21 If patients develop these hematologic AEs, HCPs should assess whether holding the therapy would be appropriate and consider resuming at a lower dose when the symptoms or laboratory abnormalities have resolved.
Based on clinical experience, patients receiving niraparib or rucaparib should be monitored weekly for hematologic AEs during the first month until it is clear that they can tolerate the starting dose, and then they can be monitored monthly.19,21 An individualized starting dose for niraparib has been developed to help prevent or mitigate the potential for hematologic AEs. Based on the prescribing information for niraparib, the recommended starting dose is 200 mg/day in patients who weigh <77 kg (<170 lb) or if their baseline platelet count is <150,000/μL. Patients receiving olaparib can be monitored monthly.
In platinum-refractory ovarian cancer, use of mirvetuximab soravtansine—a novel antibody‒drug conjugate against folate receptor α—can lead to ocular toxicity, for example, corneal inflammation, dry eye, blurry vision, and eye pain. HCPs should encourage patients to report any new or worsening vision changes or eye pain while taking this agent.
Maria Avila-Wallace, NP:
We evaluate and recommend PARP inhibitor therapy to all of our patients with ovarian cancer. Patients also may receive combination therapy with bevacizumab in the maintenance setting if they previousy received bevacizumab as treatment; this potentially could increase the likelihood and intensity of AEs. Consent for treatment regarding mitigation strategies for expected AEs is done in person by an HCP in our clinic. Adherence to oral therapy and recommended dosing and accurate reporting of AEs can be challenging and time-consuming in older patients, patients with multiple comorbidities, patients with low levels of education, non‒English speaking patients, patients with multiple social stressors, and patients with limited personal resources.
Patients are seen weekly at initiation of PARP inhibitor therapies, monitored for hematologic and other constitutional toxicities, and monitored for the need for urgent care visits; the addition of supportive therapies such as IV fluids, analgesia, and electrolyte supplementation; and reinforcement of previous treatment-related education.
Special Considerations for Managing AEs of Therapies in Patients With Cervical Cancer
Maria Avila-Wallace, NP:
In my practice, patients with cervical cancer often present with advanced disease. Of note, these patients are identified as high risk because of suboptimal or no previous screening, complex issues with access to care, being lost to follow-up in colposcopy clinics, recent immigration status, and missed opportunities for vaccination and other preventive strategies.
The standard of care for advanced cervical cancer may consist of weekly chemotherapy and daily radiation for 5-6 weeks. This is a difficult regimen with challenges in tolerability, although it is routinely and frequently completed with adequate multidisciplinary support. Treatment could lead to vaginal narrowing, vesicovaginal or rectovaginal fistulas, sexual and urinary dysfunction, and a negative impact on quality of life during and after treatment. These are critical issues that I frequently address with patients during treatment, surveillance and survivorship visits, and multidisciplinary management that includes radiation oncology and urogynecology.
Recurrent cervical cancer may require pelvic exenteration in selected patients or salvage therapy in others. Chemotherapy together with immunotherapies is also an option. Unfortunately, therapies for recurrent cervical cancer are meant to extend life but are not necessarily a means to a cure.
Eva Y. Pan, PharmD, BCOP:
The patients we see with cervical cancer are representative of the late-stage, advanced, or recurrent cervical cancer population. These are often young patients who have poor or no social support, and they may have a history of drug use and/or low socioeconomic status. Patients who relapse following platinum-based chemotherapy—and more recently platinum-based chemotherapy plus pembrolizumab with or without bevacizumab1—could receive tisotumab vedotin, which is an antibody‒drug conjugate targeting tissue factor.22
Tisotumab vedotin represents an exciting new option in the management of relapsed, persistent, or recurrent disease after progression of platinum-based chemotherapy with or without pembrolizumab. However—and as shown in the figure on the right—tisotumab vedotin is associated with ocular toxicity risk. We must talk to patients about implementing an AE mitigation and eye care strategy to maximize the therapeutic benefit of tisotumab vedotin while minimizing the potential for AEs. It is important to educate both nurses and patients on how to mitigate risk, manage ocular AEs, and mention that before each infusion of tisotumab vedotin, patients need to see an eye specialist (ophthalmologist/optometrist) to assess any changes in their vision. Patients also should be counseled to avoid contact lenses and anything that could cause eye irritation throughout treatment with tisotumab vedotin. Patients also may experience new or worsening peripheral neuropathy while receiving tisotumab vedotin.
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